Localization of stuttering based on causal brain lesions

Abstract

Stuttering affects approximately 1 in 100 adults and can result in significant communication problems and social anxiety. It most often occurs as a developmental disorder but can also be caused by focal brain damage. These latter cases may lend unique insight into the brain regions causing stuttering. Here, we investigated the neuroanatomical substrate of stuttering using three independent datasets: (i) case reports from the published literature of acquired neurogenic stuttering following stroke (n = 20, 14 males/six females, 16-77 years); (ii) a clinical single study cohort with acquired neurogenic stuttering following stroke (n = 20, 13 males/seven females, 45-87 years); and (iii) adults with persistent developmental stuttering (n = 20, 14 males/six females, 18-43 years). We used the first two datasets and lesion network mapping to test whether lesions causing acquired stuttering map to a common brain network. We then used the third dataset to test whether this lesion-based network was relevant to developmental stuttering. In our literature dataset, we found that lesions causing stuttering occurred in multiple heterogeneous brain regions, but these lesion locations were all functionally connected to a common network centred around the left putamen, including the claustrum, amygdalostriatal transition area and other adjacent areas. This finding was shown to be specific for stuttering (PFWE < 0.05) and reproducible in our independent clinical cohort of patients with stroke-induced stuttering (PFWE < 0.05), resulting in a common acquired stuttering network across both stroke datasets. Within the common acquired stuttering network, we found a significant association between grey matter volume and stuttering impact for adults with persistent developmental stuttering in the left posteroventral putamen, extending into the adjacent claustrum and amygdalostriatal transition area (PFWE < 0.05). We conclude that lesions causing acquired neurogenic stuttering map to a common brain network, centred to the left putamen, claustrum and amygdalostriatal transition area. The association of this lesion-based network with symptom severity in developmental stuttering suggests a shared neuroanatomy across aetiologies.

Keywords: acquired neurogenic stuttering; amygdala; claustrum; lesion network mapping; persistent developmental stuttering; putamen.

Figure 1

Lesion maps of the literature cohort. Numbers correspond to cases listed in Supplementary Table 1 and represent the 20 cases with stroke-induced neurogenic stuttering identified in the published literature.

Figure 2

Lesion network mapping in the literature cohort. (A) Lesion locations for each of the 20 cases served as the input for the lesion network analysis. For each case, an individual lesion network map was created using a normative connectome, resulting in a map of brain networks typically connected to the focal brain lesion location. Individual lesion network maps were thresholded at T > 5 corresponding to P_FWE < 0.05. Positive associations are shown in red-yellow, negative associations in blue-light blue. (B) Lesion network maps of the 20 cases were overlaid and thresholded at ≥80% overlap to show regions connected to most of the lesion locations (i.e. regions sensitive to stuttering). (C) To identify regions specific for stuttering, the 20 acquired stuttering cases and 169 stroke controls were compared (whole brain P_FWE < 0.05), followed by a conjunction analysis with B to identify areas both sensitive and specific for stuttering. Amy = amygdala; ASt = amygdalostriatal transition area; Cl = claustrum; Front = frontal; FWE = family-wise error; Occ = occipital; Pall = Pallidum; Put = putamen.

Figure 3

Lesion network mapping in the clinical cohort. (A) Lesion network maps of the 20 cases were overlaid, and thresholded at ≥90% overlap to show regions connected to most of the lesion locations (i.e. regions sensitive to stuttering). (B) To identify regions specific for stuttering, the 20 cases with neurogenic stuttering and 17 matched controls were compared (whole brain P_FWE < 0.05), followed by a conjunction analysis with B to identify areas both sensitive and specific for stuttering. Positive associations are shown in red-yellow, negative in blue-light blue. Amy = amygdala; ASt = amygdalostriatal transition area; Cl = claustrum; FWE = family-wise error; Pall = Pallidum; Put = putamen; Th = thalamus.

Figure 4

Common acquired neurogenic stuttering network. Common areas that were sensitive and specific across both neurogenic stuttering cohorts. Amy = amygdala; ASt = amygdalostriatal transition area; Cl = claustrum; Pall = Pallidum; Put = putamen.

Figure 5

Association between stuttering impact and grey matter volume in developmental stuttering. Regression analyses within the identified common acquired neurogenic stuttering network (from Fig. 4, transparent red in current figure) showed that more negative experiences with stuttering (OASES scores) were associated with increased grey matter volume in participants with persistent developmental stuttering (P_FWE < 0.05, shown in blue). ASt = amygdalostriatal transition area; Cl = claustrum FWE = family-wise error; OASES = Overall Assessment of the Speaker’s Experience of Stuttering; Pu = putamen.